Advances in Diagnostics and Drug Discovery against Resistant and Latent Tuberculosis Infection

Abstract

Latent tuberculosis infection (LTBI) represents a subclinical, asymptomatic mycobacterial state affecting approximately 25% of the global population. The substantial prevalence of LTBI, combined with the risk of progressing to active tuberculosis, underscores its central role in the increasing incidence of tuberculosis (TB). Accurate identification and timely treatment are vital to contain and reduce the spread of the disease, forming a critical component of the global strategy known as “End TB.” This review aims to examine and highlight the most recent scientific evidence related to new diagnostic approaches and emerging therapeutic treatments for LTBI. While prevalent diagnostic methods include the tuberculin skin test (TST) and interferon gamma release assay (IGRA), WHO’s approval of two specific IGRAs for Mycobacterium tuberculosis (MTB) marked a significant advancement. However, the need for a specific test with global application viability has propelled research into diagnostic tests based on molecular diagnostics, pulmonary immunity, epigenetics, metabolomics, and a current focus on next-generation MTB antigen-based skin test (TBST). It is within these emerging methods that the potential for accurate distinction between LTBI and active TB has been demonstrated. Therapeutically, in addition to traditional first-line therapies, anti-LTBI drugs, anti-resistant TB drugs, and innovative candidates in preclinical and clinical stages are being explored. Although the advancements are promising, it is crucial to recognize that further research and clinical evidence are needed to solidify the effectiveness and safety of these new approaches, in addition to ensuring access to new drugs and diagnostic methods across all health centers. The fight against TB is evolving with the development of more precise diagnostic tools that differentiate the various stages of the infection and with more effective and targeted treatments. Once consolidated, current advancements have the potential to transform the prevention and treatment landscape of TB, reinforcing the global mission to eradicate this disease.

Activity of Bacteriophage D29 Loaded on Nanoliposomes against Macrophages Infected with Mycobacterium tuberculosis

“…Interestingly, the results showed effective activity against latent MTB, which is beneficial given the specificity of this system. Latent MTB, unlike active MTB, has several survival properties in extreme conditions, allowing it to enter a state of dormancy capable of surviving in the absence of nutrients and oxygen, latent MTB being the most difficult phase of tuberculosis to detect and treat [63]. Recently our laboratory reported that nanoparticulate systems would be capable of eradicating multi-and extremely RIF-resistant MTB through multiple attacks, which would be favorable for future research into nanosystems and the use of conjugation or surface modification to further improve the targeted administration [64].…”

Breaking barriers: The potential of nanosystems in antituberculosis therapy

“…In this environment, naïve CD4 + cells, once stimulated by interleukin-12 (IL-12), differentiate into T helper 1 (TH1) cells, furthering the immune response ( Fig. 2 ) [ [56] , [57] , [58] ].

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Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy

“…The National Tuberculosis Controllers Association and CDC updated treatment guidelines for LTBI in 2020 are: weekly INH plus RFP for three months, daily RIF for four months or daily INH plus RIF for three months, and the alternative regimen is daily INH for six or nine months [ 185 ]. Due to the increasing resistance of LTBI to the above drugs, the development of new drugs and improved treatment options is imminent, and there are many candidates against LTBI in clinical trials, such as sutezolamide, delpazolid, telacebec, OPC-167832, SQ 109 [ 186 ], tafenoquine [ 187 ], and so on. Notably, Rv0467 , encoding isocitrate lyase (ICL), is a drug target for the treatment of latent TB, but there is no ICL inhibitor that has reached clinical trials [ 188 ].…”