There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis.
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http://dx.doi.org/10.1128/Spectrum.00481-21 | DOI Listing |
BMJ Open
January 2025
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
Introduction: Non-adherence to tuberculosis (TB) treatment poses a significant challenge to effective TB management globally and is a major contributor to the emergence of multidrug-resistant TB. Although adherence to TB treatment has been widely studied, a comprehensive evaluation of the comparative levels of adherence in high- versus low-TB burden settings remains lacking. The objective of this systematic review and meta-analysis is to assess the levels of adherence to TB treatment in high-TB burden countries compared to low-burden countries.
View Article and Find Full Text PDFLancet Glob Health
January 2025
Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, Institut National de la Santé et de la Recherche Médicale, Montpellier, France. Electronic address:
People who use drugs show a higher incidence and prevalence of tuberculosis than people who do not use drugs in areas where Mycobacterium tuberculosis is endemic. However, this population is largely neglected in national tuberculosis programmes. Strategies for active case finding, screening, and linkage to care designed for the general population are not adapted to the needs of people who use drugs, who are stigmatised and difficult to reach.
View Article and Find Full Text PDFViruses
January 2025
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity and mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), and persistent inflammation. Glutathione (GSH) has the therapeutic potential to enhance treatment outcomes by improving antibiotic efficacy, reducing inflammation, and mitigating immune dysfunction.
View Article and Find Full Text PDFMicroorganisms
January 2025
Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Pediatric tuberculosis (TB) is still challenged by several diagnostic bottlenecks, imposing a high TB burden in low- and middle-income countries (LMICs). Diagnostic turnaround time (TAT) and ease of operation to suit resource-limited settings are critical aspects that determine early treatment and influence morbidity and mortality. Based on TAT and ease of operation, this article reviews the evolving landscape of TB diagnostics, from traditional methods like microscopy and culture to cutting-edge molecular techniques and biomarker-based approaches.
View Article and Find Full Text PDFSleep Med
January 2025
Department of Pulmonology, Louvain University Center for Sleep and Wake Disorders (LUCS), University Hospitals Leuven Campus Gasthuisberg, Leuven, Belgium.
Study Objectives: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA).
Methods: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP.
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