Phylogenetic associations with demographic, epidemiological and drug resistance characteristics of Mycobacterium tuberculosis lineages in the SITVIT2 database: Macro- and micro-geographical cleavages and phylogeographical specificities

Open Access since 1 January 2015 (Open Access funded by Asian-African Society for Mycobacteriology)International audienceAims and objectives:The aim of this work was to highlight macro- and micro-geographical cleavages and phylogeographical specificities of circulating Mycobacterium tuberculosis complex (MTBC) clones worldwide to underline the demographic, epidemiological and drug resistance characteristics of major genotypic lineages.Methods:MTBC genotyping data was retrieved from an international TB genotyping database (SITVIT2) developed at Institut Pasteur de la Guadeloupe, with data on 111,635 MTBC clinical isolates from 169 countries of patient origin – almost twice as compared with the previous SITVITWEB version released in 2012. Strains typed by the most commonly used methodology for TB genotyping today were retained, i.e., spoligotyping based on the polymorphism of the direct repeat (DR) locus, and MIRU-VNTR minisatellites used in 12-, 15-, or 24-loci formats; or a combination of two methods which constitutes the gold-standard for optimal TB surveillance at the national, regional, and global levels. In-depth phylogenetical analysis of circulating strains was performed, followed by data-mining in conjunction with their geographical distribution, drug-resistance, demographic and epidemiologic characteristics. Statistical analyses were used to pinpoint geographical specificities of circulating MTBC lineages.Results:In the present work, the latest 6th version of this database was described. This study shows how the addition of new tools and supplementary information available in the SITVIT2 allowed global mapping of combined search results on MTBC genotypes, and underlined important micro- and macro-geographical cleavages for all major MTBC lineages. As an example, these results relating to the Beijing lineage (n = 10,850 strains) underlined certain specificities, e.g., (i) Japan was unique in having a majority of Beijing patients >60 years of age, while Russia was unique in having a very high proportion of male patients (male to female sex ratio of 4.93); (ii) while modern Beijing strains have spread worldwide, ancient Beijing sublineage was endemic in Japan and to a lesser extent in China; (iii) MIRU-based geo-specificity suggested probable transmission routes among certain countries; (iv) current hotspots for emergence/reemergence of Beijing strains are not necessarily countries with its highest prevalence (e.g., Japan), but rather the ones where this genotype is associated with a younger age of patients, high demography/population density, and drug-resistant TB (such as China, Indian sub-continent, and South-East Asian countries), etc. The specificities for other lineages will be further emphasized as well.Conclusions:This research was focused to improve the in-depth phylogenetic characterization of MTBC lineages in conjunction with epidemiological analysis of circulating clones to generate evidence-based geographical mapping of predominant clinical isolates of tubercle bacilli causing the bulk of the disease both at the country and regional levels. Further superimposition of these maps with socio-political, economical, and demographical characteristics available through Geographic Information Systems (GIS) allows access to a precise view of prevailing disparities as seen at the level of the United Nation’s sub-regional stratification. An in-depth comprehension of these disparities and drawbacks is important to take appropriate actions by decision-makers and public health authorities alike, in order to better monitor, understand and control the tuberculosis epidemic worldwide