Characterization of genetic diversity and clonal complexes by whole genome sequencing of Mycobacterium tuberculosis isolates from Jalisco, Mexico.

Whole genome sequencing (WGS) analysis in tuberculosis allows the prediction of drug-resistant phenotypes, identification of lineages, and to better understanding of the epidemiology and transmission chains. Nevertheless the procedure has been scarcely assessed in Mexico, in this work we analyze by WGS isolates of Mycobacterium tuberculosis circulating in Jalisco, Mexico. Lineage and phylogenetic characterization, drug resistant prediction, "in silico" spoligotyping determination, were provided by WGS in 32 M. tuberculosis clinical isolates. Lineage 4 (L4), with 28 isolates (87%) and eleven sublineages was dominant. Forty SNPs and INDELs were found in genes related to first-, and second-line drugs. Eleven isolates were sensitive, seven (22%) were predicted to be resistant to isoniazid, two resistant to rifampicin (6%) and two (6%) were multidrug-resistant tuberuclosis. Spoligotyping shows that SIT 53 (19%) and SIT 119 (16%) were dominant. Four clonal transmission complexes were found. This is the first molecular epidemiological description of TB isolates circulating in western Mexico, achieved through WGS. L4 was dominant and included a high diversity of sublineages. It was possible to track the transmission route of two clonal complexes. The WGS demonstrated to be of great utility and with further implications for clinical and epidemiological study of TB in the region.

The First exploratory spatial distribution analysis of tuberculosis and associated factors in Tonala, Mexico.

INTRODUCTION: The US-Mexico region is at high risk of elevated tuberculosis (TB) incidence due to mobility and migration. Knowledge of how socio-demographic factors varies geographically, provides clues to understanding the determinants of tuberculosis and may provide guidance for regional prevention and control strategies to improve public health in Mexico. The aim of the present study was to describe the epidemiologic characteristics and spatial patterns of the incidence of tuberculosis in Tonala, Jalisco (Mexico) from 2013-2015. METHODOLOGY: The Surveillance System Database from the Health Department, complemented by information from the National Institute of Statistics and Geography, was used to obtain data for a spatial-temporal analysis of TB cases. For the geographical analysis map creation and geoinformation storing, ArcGIS software was used. RESULTS: This study sought to characterize problem areas and jurisdictional locations of TB via a spatial approach based on analyses of case distributions and individual patient variables. The study found that tuberculosis cases were dispersed throughout Tonala County and were mainly concentrated on the Guadalajara city border. The TB cases were mainly individuals between 31 and 45 years old. Most of the cases reported during the observation period were male patients, and most cases primarily had lung involvement; however, there were quite a few cases with lymph node and intestinal disease. CONCLUSION: Our findings show that TB cases are essentially located in areas close to the city of Guadalajara and that most TB cases were pulmonary cases spread throughout the whole jurisdiction.

Genetic diversity of Mycobacterium tuberculosis and transmission associated with first-line drug resistance: a first analysis in Jalisco, Mexico.

OBJECTIVES: The objectives of this study were to analyse the frequency of gene mutations associated with antitubercular drug resistance in clinical samples from the population of Jalisco State (Mexico) and to evaluate the genetic variability of Mycobacterium tuberculosis and multidrug-resistant (MDR) M. tuberculosis strains to describe the frequency of various families. METHODS: Clinical isolates of M. tuberculosis obtained from Jalisco State were analysed. Isolates were subjected to drug susceptibility testing, and mutations were characterised by sequencing, followed by genotyping using spoligotyping and mycobacterial interspersed repetitive units-variable-number of tandem repeats (MIRU-VNTR). Moreover, the prevalence of mutations was analysed by phylogenetic lineages. RESULTS: Resistant strains were analysed by sequencing of katG, inhA and rpoB genes to determine the presence of mutations associated with isoniazid and rifampicin resistance. In MDR, monoresistant and polyresistant isolates, mutations were found in 17 (54.84%) of 31 strains. Spoligotyping identified six different strain lineages [T1 (25.40%), H3 (7.94%), MANU (4.76%), X1 (3.17%), EAI5 (1.59%) and LAM1 (1.59%)], with the remaining strains identified as orphans. In additional tree-based identification, a dendrogram of spoligotype patterns generated five different similarity clusters. When combining 24-loci MIRU-VNTR and spoligotyping approaches, the results shows that there is no cluster formation, indicating low transmission of the samples. CONCLUSIONS: This study using spoligotyping and MIRU-VNTR showed that the analysed strains were not related to each other since no two identical strains were found. Families with the highest prevalence in the study were orphans followed by T family.