Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 6 Number 1 2023
REVIEWS (Open Access)
Understanding the Complexity of Latent Tuberculosis: Biology, Diagnosis, and Treatment Challenges
Most Farhana Akter 1, Md. Robiul Islam 1, Syed Atiq Hussain 1, Anwar Hossain 1, Md Sohel Rana 1*
Microbial Bioactives 6 (1) 1-8 https://doi.org/10.25163/microbbioacts.6110675
Submitted: 20 May 2023 Revised: 13 July 2023 Accepted: 21 July 2023 Published: 23 July 2023
Abstract
Latent tuberculosis infection (LTBI) represents one of the most enduring challenges in global infectious disease control, affecting nearly one-quarter of the world’s population and serving as a vast reservoir for future active tuberculosis (TB) cases. Unlike active TB, latency is characterized by the long-term persistence of Mycobacterium tuberculosis (Mtb) in a clinically asymptomatic host, maintained through a delicate balance between bacterial survival strategies and host immune containment. This systematic review and meta-analytic synthesis explores the biological, microbiological, and host-related determinants that define Mtb dormancy, with particular emphasis on metabolic downregulation, non-replicative persistence, drug tolerance, and the capacity for resuscitation. Evidence from in vitro dormancy models, animal studies, and epidemiological analyses collectively demonstrates that latent infection is not a uniform state but rather a spectrum of physiological phenotypes that differ in culturability, antibiotic susceptibility, and reactivation potential. Dormant bacilli exhibit profound tolerance to first-line antimicrobials, largely due to reduced metabolic activity and altered cellular targets, complicating both treatment and eradication efforts. Host factors—including immune competence, HIV co-infection, metabolic disease, and immunosuppressive therapies—play a decisive role in determining whether latency is maintained or progresses to active disease. Current diagnostic tools, which rely primarily on immune memory, fail to capture bacterial viability or dormancy depth, limiting their prognostic value. By integrating microbial physiology with host risk stratification, this review highlights critical gaps in diagnostics, therapeutics, and modeling approaches, and underscores the need for strategies that specifically target dormant Mtb populations to achieve durable TB control and eventual elimination.
Keywords: Latent tuberculosis; Mycobacterium tuberculosis; dormancy; non-replicating persistence; drug tolerance; reactivation risk; host immunity
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