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.
Highlights
Tuberculosis (TB) still represents a challenging and serious public health problem despite the fact that many efforts are ongoing to eradicate the disease
According to the Global report 2015 [1], as high as 9.6 million people were estimated to have fallen ill with TB in 2014 worldwide (12% co-infected with HIV) and 1.5 million people died from it; with an alarmingly increasing problem of multidrug-resistant TB (MDR-TB)
By studying a significant number of cases during a long time interval, the present study allowed for the first time an improved genotypic tracking of specific M. tuberculosis isolates circulating in the Rhône-Alpes region in order to allocate the main trends of evolution of TB
Summary
Tuberculosis (TB) still represents a challenging and serious public health problem despite the fact that many efforts are ongoing to eradicate the disease. We decided to retrospectively analyze all Mycobacterium tuberculosis complex (MTBC) strains isolated in the Rhône Alpes (France) over an eleven year period (2000–2010), for which the genotyping results were available under a pooled systematic genotyping program among various participating centers (n = 2257 isolates) This analysis was meant to characterize existing transmission patterns, assess the impact of imported vs local TB cases, and study combined genotypic, phylogenetic, epidemiologic and demographic correlations over a large timeframe. The 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
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