Use of whole genome sequencing to explore Mycobacterium tuberculosis complex circulating in a hotspot department in France

Seine-Saint-Denis is the French metropolitan department with the highest incidence of Tuberculosis (TB). Whole-genome sequencing (WGS) is still a relatively novel approach for TB strain analysis. Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in the hotspot department of the Seine-Saint-Denis. To achieve this goal, we performed WGS on 227 strains of Mycobacterium tuberculosis complex (MTBC) isolated from TB patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localisation. Clinical and demographic data were recorded for each TB patients. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated to Asian patients whereas strains isolated from pulmonary samples were associated to European patients. We observed a high lineage diversity in line with the known worldwide diversity: lineage 1 (6%), lineage 2 (5%), lineage 3 (14%), lineage 4 (68%), lineage 5 (2%), lineage 6 (2%), and bovis lineage (3%). Lineage 7 (Ethiopia) was not represented. Interestingly, lineage 3 (East Africa Central Asia) was associated to lymph-node TB. Additionally, the sensitivity of WGS to predict resistance was 100% for rifampicin, 94% for isoniazid, 100% for ethambutol and 67% for pyrazinamide. The global concordance with drug-susceptibility testing by phenotypic approach was 96.5%. Low resistance effects of some genes and new mutations associated to resistance might explain these discrepancies. In this study based on WGS, we established the circulating lineages and the drug-susceptibility trends in a hotspot region. WGS in microbiology laboratories provides an essential tool to better understand local TB epidemiology and strain circulation.