Combined Genotypic, Phylogenetic, and Epidemiologic Analyses of Mycobacterium tuberculosis Genetic Diversity in the Rhône Alpes Region, France

Abstract

BackgroundThe present work relates to identification and a deep molecular characterization of circulating Mycobacterium tuberculosis complex (MTBC) strains in the Rhône-Alpes region, France from 2000 to 2010. It aimed to provide with a first snapshot of MTBC genetic diversity in conjunction with bacterial drug resistance, type of disease and available demographic and epidemiologic characteristics over an eleven-year period, in the south-east of France.MethodsMycobacterium tuberculosis complex (MTBC) strains isolated in the Rhône-Alpes region, France (n = 2257, 1 isolate per patient) between 2000 and 2010 were analyzed by spoligotyping. MIRU-VNTR typing was applied on n = 1698 strains (with full results available for 974 strains). The data obtained were compared with the SITVIT2 database, followed by detailed genotyping, phylogenetic, and epidemiologic analyses in correlation with anonymized data on available demographic, and epidemiologic characteristics, and location of disease (pulmonary or extrapulmonary TB).ResultsThe most predominant spoligotyping clusters were SIT53/T1 (n = 346, 15.3%) > SIT50/H3 (n = 166, 7.35%) > SIT42/LAM9 (n = 125, 5.5%) > SIT1/Beijing (n = 72, 3.2%) > SIT47/H1 (n = 71, 3.1%). Evolutionary-recent strains belonging to the Principal Genetic Group (PGG) 2/3, or Euro-American lineages (T, LAM, Haarlem, X, S) were predominant and represented 1768 or 78.33% of all isolates. For strains having drug resistance information (n = 1119), any drug resistance accounted for 14.83% cases vs. 1.52% for multidrug resistance (MDR); and was significantly more associated with age group 21–40 years (p-value<0.001). Extra-pulmonary TB was more common among female patients while pulmonary TB predominated among men (p-value<0.001; OR = 2.16 95%CI [1.69; 2.77]). Also, BOV and CAS lineages were significantly well represented in patients affected by extra-pulmonary TB (p-value<0.001). The origin was known for 927/2257 patients: 376 (40.6%) being French-born vs. 551 (59.4%) Foreign-born. French patients were significantly older (mean age: 58.42 yrs 95%CI [56.04; 60.80]) than Foreign-born patients (mean age: 42.38 yrs. 95%CI [40.75; 44.0]).ConclusionThe study underlined the importance of imported TB cases on the genetic diversity and epidemiologic characteristics of circulating MTBC strains in Rhône-Alpes region, France over a large time-period. It helps better understand intricate relationships between certain lineages and geographic origin of the patients, and pinpoints genotypic and phylogenetic specificities of prevailing MTBC strains. Lastly, it also demonstrated a slow decline in isolation of M. africanum lineage in this region between 2000 and 2010.

Strain-specific estimation of epidemic success provides insights into the transmission dynamics of tuberculosis

“…We investigated a collection of MTBC isolates representative of the Rhône-Alpes region of France, a low-MTBC prevalence area28. A total of 1,641 unique MTBC isolates (i.e.…”

Changing patterns of human migrations shaped the global population structure of Mycobacterium tuberculosis in France

“…Based on this specificity, the assignment of novel Mtb strains to lineages using molecular methods reveals the possible geographic origins of the strain’s ancestry 11 . Such approaches are essential since the connection between Mtb lineages and patients origin has a practical importance for Mtb studies in low-incidence countries where a large proportion of tuberculosis cases are imported from abroad 12 , 13 .…”

“…Based on this rationale, we performed a comprehensive phylogeographic analysis of global Mtb strains circulating in the Rhônes-Alpes region of France, a low-incidence country where two thirds of cases involve foreign-born patients 13 . Our primary objective was to contribute an in-depth description of the influence of past interactions of French and foreign populations on the current population structure of Mtb in our region.…”

Spoligotyping and whole-genome sequencing analysis of lineage 1 strains of Mycobacterium tuberculosis in Da Nang, Vietnam

“…Previous Vietnamese studies have shown that EAI isolates have irregular spoligo patterns, namely, the absence of spacers 27, 29 to 32, and 34 and the presence of spacer 26 [ 34 , 35 ], possibly because of cross-hybridization, as we observed herein. In addition, other studies have also noted that the EAI5 spoligotype SIT152 is closely related to the EAI4 spoligotype SIT139, with a difference of a single positive spacer 26 [ 36 , 37 ]. Honisch et al .…”