Use of Whole-Genome Sequencing to Explore Mycobacterium tuberculosis Complex Circulating in a Hotspot Department in France

Abstract

The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. 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 with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs.

Keywords: Mycobacterium tuberculosis; hotspot region; lineage diversity; whole-genome sequencing.

Figure 1

Global phylogeny of 227 whole-genome sequenced MTBC strains. The color codes are: pink—lineage 1, blue—lineage 2, purple—lineage 3, red—lineage 4, brown—lineage 5, green—lineage 6, gray—M. bovis lineage. The resistance status is represented for each strain with the following color code: blue—susceptible strains, yellow—strains resistant to one of the first-line drugs, orange—MDR strains (resistance to rifampicin and isoniazid). Only resistances to first-line TB drugs were considered here. MDR: multidrug-resistant.

Figure 2

Global distribution of M. tuberculosis lineages by country of origin amongst the patients included in this study. Each color represents a distinct TB lineage. The symbol of a cross on the map represents the location of the Avicenne Hospital.

Figure 3

Distribution of M. tuberculosis lineages according to the origin of the sample. EP: extrapulmonary. The asterisk correspond to the significative association between the East-African-Indian lineage and lymph node TB.