Genetic diversity and drug susceptibility of Mycobacterium tuberculosis in a city with a high prevalence of drug resistant tuberculosis from Southeast of Mexico.

BACKGROUND: Mexico is on the top five countries with the highest number of TB cases in America continent, nevertheless, information about genotypes circulating is practically unknown. Considering the above this study aims to characterize the genetic diversity of TB in the city of Veracruz, México. METHODS: A cross-sectional study was conducted among positive smear samples from patients living in Veracruz City, samples were cultured, and first-line drug profiles determined. Genotyping was made by spoligotyping and MIRU-VNTR 24 loci. Associations of lineages, clusters, and variables were also analyzed. RESULTS: Among the 202 isolates analyzed resistance to at least one drug was observed in 60 (30%) isolates and 41(20%) were multidrug-resistant. Three major lineages were identified: L4/Euro-American (88%), L1/Indo-Oceanic (9%), and L2/East Asian (3%). The Euro-American lineage included more than six sublineages, the most abundant were: H (32%), T (23%), LAM (18%), and X (12%). 140 isolates (70%) were placed in 42 SITs patterns. CONCLUSIONS: These results provide the first baseline data on the genetic structure of TB in the city of Veracruz. Sublineages H, X and LAM were predominant; however, it was founded an important diversity of genotypes that could contribute to the dispersion of TB and explain the high prevalence. This information might be useful for the development of further interventions to reduce impact of TB.

Genetic diversity of drug and multidrug-resistant Mycobacterium tuberculosis circulating in Veracruz, Mexico.

BACKGROUND: Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. METHODS: In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. FINDINGS: The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%). A total of 29 (25%) isolates were identified as orphan. The most abundant SITs were SIT53/T1 and SIT42/LAM9 with 10 isolates each and SIT50/H3 with eight isolates. Fifty-two spoligotype patterns, twenty-seven clusters and ten clonal complexes were observed, demonstrating an important genetic diversity of drug and multidrug-resistant tuberculosis isolates in circulation and transmission level of these aggravated forms of tuberculosis. Being defined as orphan or as part of an orphan cluster, was a risk factor for multidrug resistant-tuberculosis (OR 2.5, IC 1.05-5.86 and OR 3.3, IC 1-11.03, respectively). Multiple correspondence analyses showed association of some clusters and SITs with specific geographical locations. CONCLUSIONS: Our study provides one of the most detailed description of the genetic structure of drug and multidrug-resistant tuberculosis strains in southeast Mexico, establishing for the first time a baseline of the genotypes observed in resistant isolates circulating, however further studies are required to better elucidate the genetic structure of tuberculosis in region and the factors that could be participating in their dispersion.

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolates from high prevalence tuberculosis states in Mexico.

Mexico is one of the most important contributors of multidrug resistance tuberculosis (MDR-TB) in Latin-America, however little is known about the molecular characteristics of these strains. For this reason, the objective of this work was to determine the genotype and characterize polymorphisms in genes associated with resistance to rifampicin, isoniazid, and second-line drugs in isolates from two regions of Mexico with high prevalence of drug resistant tuberculosis. Clinical isolates from individuals with confirmed MDR-TB were genotyped using MIRU-VNTR 12 loci. To characterize the polymorphisms in genes associated with resistance to rifampicin, isoniazid and second-line drugs; rpoB, katG, inhA, rrs, eis, gyrA, gyrB and tlyA were sequenced. 22 (41%) of the 54 MDR-TB isolates recovered were from the state of Baja California, while 32 (59%) were from Veracruz. The results show the katGS315T mutation was observed in 20% (11/54) of the isolates, while rpoBS315L was present in 33% (18/54). rrs had three polymorphisms (T1239C, ntA1401C and ntA1401G), gyrB presented no modifications, whereas gyrA showed five (S95T, F60Y, A90V, S91P and P124A), eis two (G-10A and A431G) and tlyA one (insertion at codon 67). Only 20% (11/54) of isolates were confirmed as MDR-TB by sequencing, and no mutations at any of the genes sequenced were observed in 43% (23/54) of the strains. Two isolates were recognized with the proper set of mutations like pre-XDR and one was XDR-TB. Eighteen isolates were classified as orphans and the remaining thirty-six were distributed in fourteen lineages, the most frequent were S (11%), Haarlem (9%), Ghana (9%) and LAM (7%). Out of the fourteen clusters identified, seven included unknown genotypes and nine had lineages. This is one of the most detailed analyses of genotypic characteristics and mutations associated with drug resistance to first and second-line drugs in MDR-TB isolates from Mexico. An important genetic variability and significant discrepancy between phenotypic tests and polymorphisms was observed. Our results set the need to screen additional loci as well as implement a molecular epidemiological surveillance system of MDR-TB in the country.

A first insight into the genetic diversity of Mycobacterium Tuberculosis in Veracruz, Mexico.

OBJECTIVE/BACKGROUND: Tuberculosis (TB) remains one of the most important infectious diseases. Although Mexico is one of the Latin American countries with the largest contribution to these statistics, there are few reports that describe the genotypic characteristics of TB. The aim of this study was to use the MIRU-VNTR-24 loci to analyze the genetic diversity of M. tuberculosis circulating in the state of Veracruz, Mexico. METHODS: Here, we analyze by MIRU-VNTR-24 loci 80 clinical isolates from individuals with confirmed TB from Veracruz México, also clinical and epidemiological variables were recovered and analyzed. RESULTS: Of the individuals included in the analyses 65% were from men with an average age of 42 (± 17) years, 17% and 6% were drug and multi-drug resistant. 88% of the isolates were included in 20 clusters, of which 52% were classified into twelve orphan clusters and the remaining 37% were distributed among eight lineages: LAM (10%), EAI (9%), Haarlem (8%), H37Rv (4%), S (4%) and TUR (2%). CONCLUSION: An important diversity of lineages and unknown genotypes was identified; however, more studies are necessary in order to understand the characteristics of the genotypes displayed in the region. There is no doubt regarding the need for a molecular epidemiological surveillance system that can help to evaluate the dynamics of genotypes circulating in the country and support strategies for the prevention and management of populations affected by TB.