Active Case-Finding: An Effective Solution for Tuberculosis Detection in Vulnerable Groups - The Romanian Experience.

Introduction: Tuberculosis (TB) remains a global health challenge, requiring enhanced active case finding (ACF) through screening strategies. This study assesses the effectiveness of such an approach in locating TB cases among vulnerable groups, such as homeless persons, injecting drug users, those detained in prison, and people living in rural areas. Methods: The study focuses on socio-economic characteristics and TB detection rates across Romanian counties using modern techniques including computer-aided detection of lesions on chest X-ray and GeneXpert tests. Results: The results highlight the disproportionate burden of TB in vulnerable groups, by revealing significant differences in TB detection rates between regions. Notably, the TB detection rates among these vulnerable groups (250.85 per 100,000 population) are five times higher than the national incidence rate (46.1). Discussion: These findings underscore the imperative integration of ACF into National TB Program to provide customized and efficient solutions for diverse vulnerable groups, thereby informing crucial public health initiatives and interventions.

A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis.

Background: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. Objective: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Methods: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. Results: A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 - 0.84). Conclusions: We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted.