Description of the population structure and genetic diversity of tuberculosis in Estado de México, a low prevalence setting from Mexico

Zenteno-Cuevas, Roberto; Mendoza-Damián, Fabiola; Muñoz, Irving Cansino; Enciso-Moreno, Leonor; Perez-Navarro, Lucia Monserrat; Ramírez-Hernández, Ma. Dolores; Vázquez-Medina, Karen; Widrobo-García, Lorena; Lauzardo, Michael; Enciso-Moreno, José Antonio

doi:10.1111/apm.12312

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…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.…”

Section: Discussionmentioning

confidence: 88%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Background Whole genome sequencing (WGS) has been proposed as a tool for diagnosing drug resistance in tuberculosis. However, reports of its effectiveness in endemic countries with important numbers of drug resistance are scarce. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico. Methods WGS analysis was performed in 81 tuberculosis positive clinical isolates with a known phenotypic profile of resistance against first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin). Mutations related to drug resistance were identified for each isolate; drug resistant genotypes were predicted and compared with the phenotypic profile. Genotypes and transmission clusters based on genetic distances were also characterized. Findings Prediction by WGS analysis of resistance against isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin showed sensitivity values of 84%, 96%, 71%, 75% and 29%, while specificity values were 100%, 94%, 90%, 90% and 98%, respectively. Prediction of multidrug resistance showed a sensitivity of 89% and specificity of 97%. Moreover, WGS analysis revealed polymorphisms related to second-line drug resistance, enabling classification of eight and two clinical isolates as pre- and extreme drug-resistant cases, respectively. Lastly, four lineages were identified in the population (L1, L2, L3 and L4). The most frequent of these was L4, which included 90% (77) of the isolates. Six transmission clusters were identified; the most frequent was TC6, which included 13 isolates with a L4.1.1 and a predominantly multidrug-resistant condition. Conclusions The results illustrate the utility of WGS for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region. They also demonstrate the feasibility of this procedure for use as a tool to support the epidemiological surveillance of drug- and multidrug-resistant tuberculosis.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Little information is available on the molecular epidemiology in Mexico of Mycobacterium species. However, the published data report a variety of lineages that are prevalent in the surveyed regions ( Lopez-Rocha et al 2013 , Vera-Cabrera et al 2014 , Flores-Treviño et al 2015 , Zenteno-Cuevas et al 2015 ). While it is clear that T2D constitutes a risk for the development of TB, the immunological abnormalities that contribute to this event and the influence of the virulence of Mtb strains are less clear.…”

Section: Discussionmentioning

confidence: 99%

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

López-López

Martinez

García-Hernández

et al. 2018

Mem. Inst. Oswaldo Cruz

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BACKGROUND Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known.OBJECTIVES To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection.METHODS We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence. The levels of cell surface markers for activation secreted cytokines and chemokines, bacterial association, and intracellular bacterial growth were evaluated.FINDINGS The expression levels of HLA-DR, CD80, and CD86 were low while those of of PD-L1 were high in uninfected MDMs derived from patients with diabetes; as a result of Mtb infection, changes were only observed in the expression levels of PD-L1. The levels of cytokines (e.g., IL-6, IL-1β, IL-10, and IL-12) and chemokines (e.g., MCP-1, MIG, and RANTES) are perturbed in MDMs derived from patients with diabetes, both before infection and in response to Mtb infection. In response to the more virulent Mtb strains, the levels of association and bacterial clearance were diminished in MDMs derived from patients with diabetes.CONCLUSIONS T2D affects the basal activation state of the macrophages and its capacity to respond and control Mtb infection.

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“…According to the global TB report by the WHO, 22,869 new cases of TB were reported in 2016 in Mexico, with an incidence of 22/100,000 inhabitant and 610 cases of MDR-TB [ 1 ], and according to the Pan American Health Organization (PAHO) is placed as one of the five countries with more contributions of DR-TB and MDR-TB cases in Latin America [ 13 ]. However, there is limited data on the genotypic characteristics of the TB strains in circulation [ 14 – 16 ], including the drug and multidrug resistant isolates [ 14 , 17 – 20 ]. Moreover, there is limited data on the association between TB lineages in circulation and the clinical, epidemiological and drug resistant profiles of these isolates [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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Description of the population structure and genetic diversity of tuberculosis in Estado de México, a low prevalence setting from Mexico

Cited by 14 publications

References 27 publications

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

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

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

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

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