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

Abstract

BackgroundMexico 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.MethodsIn this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs.FindingsThe 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.ConclusionsOur 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.

Whole genomic sequencing as a tool for diagnosis of drug and multidrug-resistance tuberculosis in an endemic region in Mexico

“…For these reasons, Veracruz is positioned as one of the most significant contributors to the DR-TB and MDR-TB problem in Mexico. The epidemiological characteristics of the population included in this study, such as a high proportion of individuals with T2DM (36%) and primary treatment (47%), reflect previous reports for the region [24,25,30,42] and confirm the influence of T2DM as an important factor in the development of DR-TB and MDR-TB, as well as highlighting the difficulties for diagnosis, control and preventive management of DR-TB by the health agencies as well as evidencing the urgent need to develop new diagnostic procedures.…”

“…While it was only a relatively small number of isolates studied, four lineages were identified; 90% (76) were placed in L4 (Euro-American), confirming the predominance of this lineage in the population [24,25,42,55,56] and the presence of the “founder effect”, where the predominance of specific lineages seems to limit the dispersion of new or less frequent lineages [56–58]. Twenty-six (32%) isolates were located within six transmission clusters, of which two were particularly noteworthy: i) the TC1, which included the only two isolates with L3 (CAS) and ii) the TC6, comprising 13 (17%) MDR-TB isolates with sub-lineage 4.1.1 (X), including one isolate identified as pre-XDR-TB and another as XDR-TB.…”

“…Twenty-six (32%) isolates were located within six transmission clusters, of which two were particularly noteworthy: i) the TC1, which included the only two isolates with L3 (CAS) and ii) the TC6, comprising 13 (17%) MDR-TB isolates with sub-lineage 4.1.1 (X), including one isolate identified as pre-XDR-TB and another as XDR-TB. These CAS and X lineages are rarely referred in Mexico, particularly with such a strong tendency towards drug resistance [24,25,42,55,59] and additional studies will be necessary to determine the extension of this sub-lineages in the population.…”

Spoligotyping of Mycobacterium tuberculosis isolates using Luminex®-based method in Lebanon

“…Interestingly, the high prevalence of orphan MTB genotypes (32.6%) detected in our study could be attributed to the use of spoligotyping as a sole technique, comparable to what was reported in other studies [30,40]. This points out the need for coupling spoligotyping to other techniques, such as Variable Number of Tandem Repeat (VNTR) analysis and WGS to improve taxonomical assignments and possibly to reveal antituberculosis drug resistance profile.…”

Usefulness of 3’- 5’ IS6110-RFLP genotyping and spoligotyping of Mycobacterium tuberculosis isolated in a tertiary hospital: a retrospective study detecting unsuspected epidemiological events

“…Moreover, the data corroborate other studies suggesting that all-major circulating families are associated to resistance in a given geographic area 24 , 25 . In a recent report concerning strains isolated from Veracruz, Southeastern Mexico, the T lineage was predominant and 8/10 samples of the T1 sublineage were SIT 53 multidrug-resistant 26 . Similarly, 47% (27/58) of all drug resistant isolates detected in the present study belonged to the T superfamily, with T1 contributing to most cases (22/27, 78.6%).…”