Tuberculosis treatment strategies aim to reduce early mortality by initiating anti-tuberculosis treatment in individuals at high risk of death from undiagnosed TB. Compared to starting anti-tuberculosis treatment on clinical or mycobacteriological grounds,4.4-31.4% more individuals were eligible for anti-tuberculosis treatment,5.5-25.4% of deaths were averted and 10.9-57.3% of incident TB cases were prevented under empirical anti-tuberculosis treatment strategies. The proportion receiving any anti-tuberculosis treatment during the first 6 months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% and 51.3%, under the PrOMPT, REMEMBER and pragmatic approach, respectively. The impact of empirical anti-tuberculosis treatment strategies depends greatly on the eligibility criteria chosen. The additional strain placed on anti-tuberculosis treatment facilities and the relatively limited impact of some empirical TB strategies raise the question as to whether the benefits will outweigh the risks at population level. Despite the advent of new diagnostics, drugs and regimens, tuberculosis (TB) remains a global public health threat.A significant challenge for TB control efforts has been the monitoring of TB therapy and determination of TB treatment success. We review the pipeline of molecular technologies and assays that serve as suitable substitutes for current culture-based readouts for treatment response and outcome with the potential to change TB therapy monitoring and accelerate drug development. An effective 6-month therapy with isoniazid, rifampin, and pyrazinamide is safe for childhood tuberculosis.Varying schedules and direct observation ensure adherence but do not solve all problems. Drug resistance requires special consideration for children. HOST IMMUNE manipulation may be the next frontier. Novel antibiotics based on human AMPs displaying a rapid and multifaceted mechanism, with reduced toxicity, should significantly contribute to reverse the tide of antimycobacterial drug resistance.Despite of the serious effort that has been applied to develop effective antitubercular chemotherapies, the potential of antimicrobial peptides (AMPs) remains underexploited. We should not underestimate our endogenous antimicrobial proteins and peptides as ancient players of the human host defense system.A better understanding on the mechanisms of action of human endogenous peptides should ensure the basis for the best guided design of novel antitubercular chemotherapeutics. Tuberculosis (TB) continues to be a devastating infectious disease and remerges as a global health emergency due to an alarming rise of antimicrobial resistance to its treatment. In this context, we are confident that novel antibiotics based on human AMPs displaying a rapid and multifaceted mechanism, with reduced toxicity, should significantly contribute to reverse the tide of antimycobacterial drug resistance. Achieving global control of tuberculosis (TB) is challenging due to increasing multidrug resistance and mortality. Efforts are ongoing to develop new vaccines, diagnostics and drugs. Shorter, optimized treatment regimens and drug delivery, new antimicrobials and immunotherapy could improve cure rates.Recent data show chronic worm infection and micronutrient deficiencies like vitamin D and arginine are potential intervention areas to optimize immunity. Nutritional supplementation to increase nitric oxide and vitamin D functions and deworming to reduce immunosuppressive regulatory T lymphocyte effects may suit highly endemic areas better than cytokine therapy.We focus on human TB immunity and how treatment like immunotherapy and nutrition could enhance the host response for effective treatment. Autophagy is a cellular process critical for maintaining cellular integrity and function.When the host innate defensive system is manipulated by Mtb for its survival and dissemination, the host develops disease conditions that are hard to overcome. The host intrinsic factors also contributes to the poor efficacy of anti-mycobacterial drugs and to the emergence of drug resistance.Hence, strengthening the immune repertoire involved in combating Mtb through host-directed therapeutics (HDT) can be one of the approaches for effective bacterial killing and clearance of infection/disease. Recently, more scientific research has been focused toward HDT strategies that empowers host cells for effective killing of Mtb,reduce the duration of treatment and/or alleviates the development of MDR/XDR, since Mtb cannot develop resistance against a drug that targets the host cell function. In this review, we summarize the role of autophagy in Mtb pathogenesis, the mTOR pathway and, modulating the mTOR pathway with inhibitors as potential adjunctive HDT, in combination with standard anti-TB antibiotics, to improve the outcome of current TB treatment. Tuberculosis (TB) is a poverty infectious disease that affects millions of people worldwide.Meta-analyses were performed with 9 randomized controlled trials. Pooled results showed that SPS was associated with TB treatment success, cure of TB patients and with reduction in risk of TB treatment default.We did not detect effects of SPS on the outcomes treatment failure and death. These findings revealed that SPS might improve TB treatment outcomes in lower-middle-income economies or countries with high burden of this disease. However, the overall quality of evidences regarding these effect estimates is low and further well-conducted randomized studies are needed. We apply optimal control theory to a tuberculosis model by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions. Numerical simulations are given using data from Angola. A significant increase in cure rates, by 18% with DOTS and by 16% with patient education and counselling, was observed. In addition, the default rate decreased by 49% with DOTS, by 26% with financial incentives and by 13% with patient education and counselling. Use of DOTS and patient education/counselling significantly improved cure rates; DOTS, patient education/counselling and financial incentives led to a reduction in the default rate. Dispersive drug resistance has become a serious issue in tuberculosis treatment. New drugs are urgently needed to combat drug-resistant TB.Whole cell screening and structure–activity relationship studies led to the detection of chemotypes effective against multidrug-resistant TB. Further analysis revealed that the choice of growth medium greatly impacts the discovery of useful anti-TB drugs. Efforts are ongoing to repurpose existing drugs for treating drug-resistant TB. The development of new treatments remains challenging, but promising avenues include exploring different drug targets and improving treatment regimens. Our results support the implementation of LF‐LAM to be used in conjunction with other WHO‐recommended tuberculosis diagnostic tests to assist in the rapid diagnosis of tuberculosis in people living with HIV. Despite significant efforts, tuberculosis (TB) remains prevalent due to limitations of current treatments. Recent work suggests directly targeting host factors may benefit TB treatment. Such host-directed therapeutics (HDTs) focus on host-pathogen interactions and may be more effective than currently approved drugs, limited by long treatment and drug resistance. HDT targets include host cytokines, immune checkpoints, immune cell functions, essential enzymes. This reviews promising HDT examples and approaches for development.