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( ) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.
View Article and Find Full Text PDFThe Development of a Vocational Rehabilitation Program to Assist Individuals With MDRTB and TB in Returning to Work.
Occup Ther Int
January 2025
Occupational Therapy Department, University of the Western Cape, Cape Town, South Africa.
Individuals diagnosed with tuberculosis (TB) and multidrug-resistant (MDR) TB may struggle to return to work after they have completed a rehabilitation program. Multidrug-resistant tuberculosis (MDRTB) has been seen as a condition that is resistant to treatment, hence causing individuals to be economically in-active for considerable periods of time. The aim of the current study was to explore the views of individuals living with MDRTB, individuals with TB, and health professionals treating individuals with TB and MDRTB about the development of a vocational rehabilitation program.
View Article and Find Full Text PDFObjectives: This study aimed to investigate genotypic characteristics and drug resistance profiles of complex (Mtbc) strains isolated from patients with suspected tuberculosis (TB) in Gabon.
Methods: We performed whole genome sequencing of 430 Mtbc strains cultured between 2012 and 2022. Phylogenetic strain classification, genomic resistance prediction, and cluster analysis were also performed.
Post-TB sequelae in adolescent pulmonary TB survivors.
IJTLD Open
January 2025
Division of Respirology, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/Dr Hasan Sadikin General Hospital, Bandung, Indonesia.
Objective: To compare the persistent clinical symptoms, chest X-ray (CXR), spirometry and echocardiography results in adolescent survivors of drug-susceptible (DS) and drug-resistant (DR) pulmonary TB (PTB).
Methods: This retrospective cohort study was conducted in 52 adolescent PTB survivors. We compared persistent clinical symptoms, CXR, spirometry and echocardiography in DS-TB and DR-TB survivors.
Background: Drug-resistant TB (DR-TB) remains a public health concern in Kenya, with an estimated 2,500 individuals acquiring DR-TB annually. Despite significant progress in DR-TB management, the treatment success rate (TSR) in 2021 stood at 77%, falling short of the 85% target. This low TSR occurs amidst a complex range of treatment challenges, including psychosocial factors.
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