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Tuberculosis (TB) is a major public health problem, with nearly 10 million new cases and millions of deaths each year. Around 10% of these cases are in children, but only a fraction receive proper diagnosis and treatment. The spread of drug-resistant (DR) strain of TB has made it difficult to control, with only 60% of patients responding to treatment. Multi-drug resistant TB (MDR-TB) is often undiagnosed in children due to lack of awareness or under-diagnosis, and the target for children’s DR-TB treatment has only been met in 15% of goals. New medications such as bedaquiline and delamanid have been approved for treating DR-TB. However, due to age and weight differences, adults and children require different dosages. The availability of child-friendly formulations is limited by a lack of clinical data in children. This paper reviews the development history of these drugs, their mechanism of action, efficacy, safety potential problems and current use in treating DR-TB in children.

Drug-resistant tuberculosis (DR-TB) in children is a growing global health concern, This review provides an overview of the current epidemiology of childhood TB and DR-TB, including prevalence, incidence, and mortality. We discuss the challenges in diagnosing TB and DR-TB in children and the limitations of current diagnostic tools. We summarize the challenges associated with treating multi-drug resistance TB in childhood, including limitations of current treatment options, drug adverse effects, prolonged regimens, and managing and monitoring during treatment. We highlight the urgent need for improved diagnosis and treatment of DR-TB in children. The treatment of children with multidrug-resistant tuberculosis will be expanded to include the evaluation of new drugs or new combinations of drugs. Basic research is needed to support the technological development of biomarkers to assess the phase of therapy, as well as the urgent need for improved diagnostic and treatment options.

Understanding how Mycobacterium tuberculosis has evolved into a professional pathogen is helpful in studying its pathogenesis and for designing vaccines. We investigated how the evolutionary adaptation of M. smegmatis mc251 to an important clinical stressor H2O2 allows bacteria to undergo coordinated genetic mutations, resulting in increased pathogenicity. Whole-genome sequencing identified a mutation site in the fur gene, which caused increased expression of katG. Using a Wayne dormancy model, mc251 showed a growth advantage over its parental strain mc2155 in recovering from dormancy under anaerobic conditions. Meanwhile, the high level of KatG in mc251 was accompanied by a low level of ATP, which meant that mc251 is at a low respiratory level. Additionally, the redox-related protein Rv1996 showed different phenotypes in different specific redox states in M. smegmatis mc2155 and mc251, M. bovis BCG, and M. tuberculosis mc27000. In conclusion, our study shows that the same gene presents different phenotypes under different physiological conditions. This may partly explain why M. smegmatis and M. tuberculosis have similar virulence factors and signaling transduction systems such as two-component systems and sigma factors, but due to the different redox states in the corresponding bacteria, M. smegmatis is a nonpathogen, while M. tuberculosis is a pathogen. As mc251 overcomes its shortcomings of rapid removal, it can potentially be developed as a vaccine vector.

Objectives: Ginsenosides Rb1 (Rb1) could form micelles in aqueous solutions. Self-assembled Rb1 micelles could potentially be utilized as ocular drug delivery system, and it was postulated that the encapsulation of a medicine within Rb1 micelles might strengthen the drug’s therapeutic action and reduce side effects. Methods: Diclofenac-loaded Rb1 micelles (Rb1-Dic micelles) were formulated, optimized, and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vivo corneal permeation, and in vivo anti-inflammatory efficacy. Results: Rb1 self-assembled into micelles with ultra-small particle size (