Background: Accurate drug susceptibility testing (DST) of (MTB) is essential for proper patient management. We investigated discordance between genotypic (Xpert MTB/RIF and MTBDR) and phenotypic (MGIT 960) methods for the detection of rifampicin (RIF) and isoniazid (INH) resistant MTB and its correlation with patient treatment outcomes in Jimma, Southwest Oromia, Ethiopia.
Methods: A retrospective study was conducted on 57 stored MTB isolates with known Xpert RIF resistance status (45 RIF resistant and 12 RIF susceptible) at Jimma University Mycobacteriology Research Center from November 2, 2021, to December 28, 2022. We did MTBDR and phenotypic DST (using the Mycobacterial Growth Indicator Tube (MGIT) system). The Xpert and MTBDR results were compared using phenotypic DST as a reference standard method. The treatment outcome was determined as per national guideline. The discordance between the genotypic and phenotypic DST was calculated using GraphPad software.
Results: Among the 57 MTB isolates, six (10.5 %) had discordant results between the two DST methods. Xpert yielded five discordant results for RIF when compared with phenotypic DST (kappa coefficient (κ) = 0.76, 95 % confidence interval 0.56-0.96). The MTBDR compared with phenotypic DST gave three discordant results for RIF (κ = 0.86, 95 % confidence interval 0.71-1.00) and three for INH (κ = 0.86, 95 % confidence interval 0.70-1.00). Compared with Xpert, MTBDR yielded lower discordance with phenotypic DST for RIF. Out of six patients with discordant results, three had unfavorable outcomes while the other three were cured. Of the three patients with unfavorable outcomes, only one patient has received an inappropriate treatment regimen. There was no correlation between unfavorable outcomes and incorrect treatment regimens due to discordant results (Χ = 0.404; P = 0.525).
Conclusions: Discordance between genotypic and phenotypic DST for RIF or INH occurred in 10.5 % of isolates. Only one patient with discordant results has received an inappropriate treatment regimen, resulting in an unfavorable outcome. The impact of parallel use of rapid molecular assay with phenotypic DST on patient treatment outcomes requires further study.
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http://dx.doi.org/10.1016/j.jctube.2023.100410 | DOI Listing |
BMC Infect Dis
January 2025
Chinese Center for Disease Control and Prevention, National Tuberculosis Reference Laboratory, No. 155 Chang Bai Road, Changping District, Beijing, 102206, People's Republic of China.
Background: Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), However, limited research exists on their clinical and strain characteristics. This study aims to investigate the correlation between these factors in TB-DM patients in Changping District. METHODS: Whole genome sequencing (WGS) and drug susceptibility tests (DST) were performed on culture-positive strains.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Centre for Tuberculosis Research, Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster 3rd Milestone, Faridabad, Haryana 121001, India.
Itaconate, an abundant metabolite produced by macrophages upon interferon-γ stimulation, possesses both antibacterial and immunomodulatory properties. Despite its crucial role in immunity and antimicrobial control, its mechanism of action and dissimilation are poorly understood. Here, we demonstrate that infection of mice with increases itaconate levels in lung tissues.
View Article and Find Full Text PDFPLoS Genet
January 2025
Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st St. SW, Rochester, Minnesota 55905, United States of America.
Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function.
View Article and Find Full Text PDFEClinicalMedicine
January 2025
School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
Background: Targeted next-generation sequencing (tNGS) is promising alternative to phenotypic drug susceptibility testing (pDST) for detecting drug-resistant tuberculosis (DRTB). This study explored the potential cost-effectiveness of tNGS for the diagnosis of DR-TB across 3 settings: India, South Africa and Georgia.
Methods: To inform WHO guideline development group (GDG) on tNGS we developed a stochastic decision analysis model and assessed cost-effectiveness of tNGS for DST among rifampicin resistance individuals.
Neurol Genet
February 2025
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Background And Objectives: Neonatal encephalopathy (NE) is characterized by an abnormal level of consciousness with or without seizures in the neonatal period. It affects 1-6/1,000 live term newborns. We applied genome sequencing (GS) in term newborns with NE to investigate the underlying genetic causes.
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