RESUMEN

Drug resistant tuberculosis (DR-TB) is an important public health issue in different parts of the world. Mycobacterium tuberculosis complex variants (MTBC vars) preferentially infect certain hosts, limiting their distribution to different ecosystems. However, MTBC vars can infect other hosts beyond their preferred target potentially contributing to persistence of drug resistance (DR) in other niches. Here, we performed a comprehensive intra-host genetic analysis for the identification of DR-related mutations among all MTBC minor vars whole genome sequences (8,095 strains) publicly available worldwide. High confidence drug-resistance mutations in katG (isoniazid), rpsL (streptomycin), pncA (pyrazinamide), rpoB (rifampicin) and gyrA (fluoroquinolones) genes were identified among intrahost minor sub-populations in 197 different strains (2.43%) belonging to vars africanum, bovis, caprae, microti, orygis and pinnipedii. In addition, a three-dimensional structure modeling analysis to assess the role of novel mutations was also performed. Our findings highlight the importance of detecting discrete intra-host populations carrying DR mutations.

Asunto(s)

Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Resistencia a Medicamentos , Ecosistema , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología

RESUMEN

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.

Asunto(s)

Análisis Espacio-Temporal , Tuberculosis/epidemiología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Ciudades/epidemiología , Demografía , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , México/epidemiología , Persona de Mediana Edad , Factores Socioeconómicos , Resultado del Tratamiento , Adulto Joven

RESUMEN

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.

Asunto(s)

Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Secuenciación Completa del Genoma/métodos , Antituberculosos/farmacología , Análisis por Conglomerados , Farmacorresistencia Bacteriana/genética , Enfermedades Endémicas , Genotipo , Humanos , México , Mutación , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia

RESUMEN

Here, we describe the molecular characterization of six human Mycobacterium bovis clinical isolates, including three multidrug resistant (MDR) strains, collected in Mexico through the National Survey on Tuberculosis Drug Resistance (ENTB-2008), a nationally representative survey conducted during 2008-2009 in nine states with a stratified cluster sampling design. The genetic background of bovine M. bovis strains identified in three different states of Mexico was studied in parallel to assess molecular relatedness of bovine and human strains. Additionally, resistance to first and second line anti-tuberculosis (TB) drugs and molecular identification of mutations conferring drug resistance was also performed. All strains were characterized by spoligotyping and 24-loci MIRU-VNTRs, and analyzed using the SITVIT2 (n = 112,000 strains) and SITVITBovis (n = 25,000 strains) proprietary databases of Institut Pasteur de la Guadeloupe. Furthermore, data from this study (n = 55 isolates), were also compared with genotypes recorded for M. bovis from USA (n = 203), Argentina (n = 726), as well as other isolates from Mexico (independent from the present study; n = 147), to determine any evidence for genetic relatedness between circulating M. bovis strains. The results showed that all human M. bovis cases were not genetically related between them or to any bovine strain. Interestingly, a high degree of genetic variability was observed among bovine strains. Several autochthonous and presumably imported strains were identified. The emergence of drug-resistant M. bovis is an important public health problem that jeopardizes the success of TB control programs in the region.

Asunto(s)

Farmacorresistencia Bacteriana Múltiple/genética , Mutación , Mycobacterium bovis/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/microbiología , Antituberculosos/uso terapéutico , Bases de Datos Genéticas , Genotipo , Humanos , México/epidemiología , Pruebas de Sensibilidad Microbiana , Repeticiones de Minisatélite , Técnicas de Diagnóstico Molecular , Mycobacterium bovis/efectos de los fármacos , Mycobacterium bovis/aislamiento & purificación , Fenotipo , Filogenia , Valor Predictivo de las Pruebas , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/transmisión

RESUMEN

Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.

Asunto(s)

Antivirales/uso terapéutico , Evolución Molecular , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/transmisión , Animales , Antivirales/efectos adversos , Progresión de la Enfermedad , Farmacorresistencia Viral , Quimioterapia Combinada , Genotipo , Hepacivirus/patogenicidad , Hepatitis C/diagnóstico , Interacciones Huésped-Patógeno , Humanos , Fenotipo , Resultado del Tratamiento

RESUMEN

Globally, hepatitis C virus (HCV) infection affects approximately 130 million people and 3 million new infections occur annually. HCV is also recognized as an important cause of chronic liver disease in children. The absence of proofreading properties of the HCV RNA polymerase leads to a highly error prone replication process, allowing HCV to escape host immune response. The adaptive nature of HCV evolution dictates the outcome of the disease in many ways. Here, we investigated the molecular evolution of HCV in three unrelated children who acquired chronic HCV infection as a result of mother-to-child transmission, two of whom were also coinfected with HIV-1. The persistence of discrete HCV variants and their population structure were assessed using median joining network and Bayesian approaches. While patterns of viral evolution clearly differed between subjects, immune system dysfunction related to HIV coinfection or persistent HCV seronegativity stand as potential mechanisms to explain the lack of molecular evolution observed in these three cases. In contrast, treatment of HCV infection with PegIFN, which did not lead to sustained virologic responses in all 3 cases, was not associated with commensurate variations in the complexity of the variant spectrum. Finally, the differences in the degree of divergence suggest that the mode of transmission of the virus was not the main factor driving viral evolution.

Asunto(s)

Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Antivirales/uso terapéutico , Niño , Coinfección/virología , Evolución Molecular , Femenino , Variación Genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/transmisión , VIH-1 , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Masculino , Polietilenglicoles/uso terapéutico , Embarazo , Complicaciones Infecciosas del Embarazo/virología , ARN Viral , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Resultado del Tratamiento

Asunto(s)

Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Epidemiología Molecular/métodos , Virosis/epidemiología , Virosis/genética , Animales , Variación Genética , Humanos , Análisis de Secuencia de ADN/métodos

RESUMEN

Tuberculosis is an important public health problem in Mexico. However, limited information about the genetic diversity of Mycobacterium tuberculosis strains circulating in the country is available. In this work, 109 multidrug-resistant (MDR) M. tuberculosis isolates collected in 23 different states of Mexico in 2003 were retrospectively characterized by spoligotyping and MIRU-VNTRs. All isolates, except for a single cluster containing two strains (subcluster E1), were split when information from the 12-loci MIRUs and spoligo-pattern was simultaneously analyzed. The discriminative power of 12-loci MIRU-VNTR and spoligotyping, by the Hunter-Gaston index, were 0.9998 and 0.9011, respectively. These findings suggest that almost all cases were epidemiologically unrelated. Instead, the genetic variations observed among these strains are suggestive of emergence of acquired drug-resistance during the course of treatment. The results suggest a high degree of genetic variability and a high frequency of SIT53 (T1 family) spoligotype among the MDR M. tuberculosis isolates included in the study.

Asunto(s)

Variación Genética , Genotipo , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibióticos Antituberculosos/farmacología , Niño , Preescolar , Análisis por Conglomerados , ADN Bacteriano , Femenino , Humanos , Masculino , México/epidemiología , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Repeticiones de Minisatélite , Tipificación Molecular , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Topografía Médica , Adulto Joven

RESUMEN

Here, we analyze the viral divergence among hepatitis C virus (HCV) chronic cases infected with genotype 1. The intrahost viral evolution was assessed by deep sequencing using the 454 Genome Sequencer platform. The results showed a rapid nucleotide sequence divergence. This notorious short-term viral evolution is of the utmost importance for the study of HCV transmission, because direct links between related samples were virtually lost. Thus, rapid divergence of HCV significantly affects genetic relatedness studies and outbreak investigations.

Asunto(s)

Variación Genética , Hepacivirus/genética , Hepatitis C Crónica/virología , Adulto , Anciano , Evolución Molecular , Femenino , Genoma Viral , Genotipo , Hepacivirus/clasificación , Hepatitis C Crónica/genética , Humanos , Interferones , Interleucinas/genética , Masculino , Persona de Mediana Edad , Filogenia , Factores de Riesgo , Análisis de Secuencia de ADN

RESUMEN

BACKGROUND: The epidemiological patterns of varicella-zoster virus (VZV) infection, which are strongly associated with climate, are characterized by more frequent infections occurring among children in temperate regions than in the tropics. In temperate regions, varicella exhibits a seasonal cyclic behavior in which the number of cases increases significantly during the winter and spring seasons, further supporting the role of environmental factors in disease transmission. However, the underlying mechanisms responsible for this distinctive behavior are not fully understood. In Mexico, information regarding the epidemiology of varicella is scarce, and the distribution of VZV infection has not been analyzed. OBJECTIVES: In this article we investigate the epidemiological patterns of varicella in Mexico and their relationship with different environmental and demographic factors. STUDY DESIGN: A retrospective study was conducted using the data reported by the National Center of Epidemiological Surveillance and Disease Control. The overall varicella incidence was calculated and associated with temperature, overcrowding, age, gender and population density. RESULTS: The epidemiology of varicella showed an intriguing pattern, in which warmer regions were characterized by higher incidences than in temperate regions. Young children were the most affected age group. There was no correlation between varicella incidence and overcrowding or population density. CONCLUSIONS: The epidemiology of varicella in Mexico significantly departs from the characteristic patterns observed in other tropical latitudes, with some features resembling those commonly associated with temperate regions.

Asunto(s)

Varicela/epidemiología , Adolescente , Adulto , Niño , Preescolar , Clima , Aglomeración , Femenino , Humanos , Incidencia , Lactante , Masculino , México/epidemiología , Densidad de Población , Estudios Retrospectivos