Abstract

Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations—isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for Mycobacterium tuberculosis latency.

Highlights

  • Tuberculosis (TB), an infection caused by the bacillus Mycobacterium tuberculosis, still remains one of the top 10 causes of death worldwide, especially in low- and lower-middleincome countries [1]

  • Despite a small share of total TB cases, the number of MDR-TB and XDR-TB cases is increasing every year (0.22 million in 2019 up from 0.20 million in 2018, and 0.17 million in 2017) [2,3,4]. Another global challenge in TB management is the ability of M. tuberculosis to cause latent infection, which can suddenly turn into active disease during the lifetime of infected individuals

  • Latent tuberculosis infection is a serious obstacle to the complete elimination of tuberculosis

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Summary

Introduction

Tuberculosis (TB), an infection caused by the bacillus Mycobacterium tuberculosis, still remains one of the top 10 causes of death worldwide, especially in low- and lower-middleincome countries [1]. Despite a small share of total TB cases, the number of MDR-TB and XDR-TB cases is increasing every year (0.22 million in 2019 up from 0.20 million in 2018, and 0.17 million in 2017) [2,3,4] Another global challenge in TB management is the ability of M. tuberculosis to cause latent infection, which can suddenly turn into active disease during the lifetime of infected individuals. Latent TB infection is diagnosed by the absence of clinical symptoms and signs and by positive tuberculin skin (TST) or interferon-gamma release assay (IGRA) blood tests. These tests/diagnostic approaches have some limitations [5]. This term is often used in the context of the in vitro model of progressive hypoxia (the Wayne model), where M. tuberculosis cells decrease metabolism and replication rate, and become phenotypically resistant to isoniazid [18]

Pathogenesis of Latent Tuberculosis Infection in Humans
In Vitro and In Vivo Models to Imitate Mycobacterium tuberculosis Latency
Alternatives for Latent Tuberculosis Infection Treatment
Early-Stage Compounds Active against Dormant and Non-Replicating Bacilli
Copper-Mediated Innate Immunity
Unknown Targets
Findings
Concluding Remarks and Future Outlook
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