RESUMO
Diarrheal diseases are a leading cause of mortality and morbidity in low- and middle-income countries. Diarrhea is associated with a wide array of etiological agents including bacterial, viral, and parasitic enteropathogens. Previous studies have captured between- but not within-country heterogeneities in enteropathogen prevalence and severity. We conducted a case-control study of diarrhea to understand how rates and outcomes of infection with diarrheagenic pathotypes of Escherichia coli vary across an urban-rural gradient in four sites in Ecuador. We found variability by site in enteropathogen prevalence and infection outcomes. Any pathogenic E. coli infection, coinfections, diffuse adherent E. coli (DAEC), enteroinvasive E. coli (EIEC), and rotavirus were significantly associated with acute diarrhea. DAEC was the most common pathotype overall and was more frequently associated with disease in urban areas. Enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) were more common in rural areas. ETEC was only associated with diarrhea in one site. Phylogenetic analysis revealed that associations with disease were not driven by any single clonal complex. Higher levels of antibiotic resistance were detected in rural areas. Enteropathogen prevalence, virulence, and antibiotic resistance patterns vary substantially by site within Ecuador. The variations in E. coli pathotype prevalence and virulence in this study have important implications for control strategies by context and demonstrate the importance of capturing within-country differences in enteropathogen disease dynamics.
Assuntos
Escherichia coli Enteropatogênica , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Humanos , Infecções por Escherichia coli/microbiologia , Estudos de Casos e Controles , Equador/epidemiologia , Filogenia , Escherichia coli Enteropatogênica/genética , Diarreia/microbiologia , Escherichia coli Enterotoxigênica/genética , Fezes/microbiologiaRESUMO
Previous studies have reported lower fecal bacterial diversity in urban populations compared with those living in rural settings. However, most of these studies compare geographically distant populations from different countries and even continents. The extent of differences in the gut microbiome in adjacent rural versus urban populations, and the role of such differences, if any, during enteric infections remain poorly understood. To provide new insights into these issues, we sampled the gut microbiome of young children with and without acute diarrheal disease (ADD) living in rural and urban areas in northern Ecuador. Shotgun metagenomic analyses of non-ADD samples revealed small but significant differences in the abundance of microbial taxa, including a greater abundance of Prevotella and a lower abundance of Bacteroides and Alistipes in rural populations. Greater and more significant shifts in taxon abundance, metabolic pathway abundance, and diversity were observed between ADD and non-ADD status when comparing urban to rural sites (Welch's t-test, P < 0.05). Collectively our data show substantial functional, diversity, and taxonomic shifts in the gut microbiome of urban populations with ADD, supporting the idea that the microbiome of rural populations may be more resilient to ADD episodes.
Assuntos
Bactérias/classificação , Bactérias/genética , Diarreia/microbiologia , Microbioma Gastrointestinal , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Doença Aguda/epidemiologia , Adolescente , Adulto , Idoso , Bactérias/isolamento & purificação , Criança , Pré-Escolar , Diarreia/epidemiologia , Equador/epidemiologia , Fezes/microbiologia , Humanos , Lactente , Recém-Nascido , Metagenômica , Pessoa de Meia-Idade , Adulto JovemRESUMO
Escherichia coli is a leading contributor to infectious diarrhea and child mortality worldwide, but it remains unknown how alterations in the gut microbiome vary for distinct E. coli pathotype infections and whether these signatures can be used for diagnostic purposes. Further, the majority of enteric diarrheal infections are not diagnosed with respect to their etiological agent(s) due to technical challenges. To address these issues, we devised a novel approach that combined traditional, isolate-based and molecular-biology techniques with metagenomics analysis of stool samples and epidemiological data. Application of this pipeline to children enrolled in a case-control study of diarrhea in Ecuador showed that, in about half of the cases where an E. coli pathotype was detected by culture and PCR, E. coli was likely not the causative agent based on the metagenome-derived low relative abundance, the level of clonality, and/or the virulence gene content. Our results also showed that diffuse adherent E. coli (DAEC), a pathotype that is generally underrepresented in previous studies of diarrhea and thus, thought not to be highly virulent, caused several small-scale diarrheal outbreaks across a rural to urban gradient in Ecuador. DAEC infections were uniquely accompanied by coelution of large amounts of human DNA and conferred significant shifts in the gut microbiome composition relative to controls or infections caused by other E. coli pathotypes. Our study shows that diarrheal infections can be efficiently diagnosed for their etiological agent and categorized based on their effects on the gut microbiome using metagenomic tools, which opens new possibilities for diagnostics and treatment.IMPORTANCEE. coli infectious diarrhea is an important contributor to child mortality worldwide. However, diagnosing and thus treating E. coli infections remain challenging due to technical and other reasons associated with the limitations of the traditional culture-based techniques and the requirement to apply Koch's postulates. In this study, we integrated traditional microbiology techniques with metagenomics and epidemiological data in order to identify cases of diarrhea where E. coli was most likely the causative disease agent and evaluate specific signatures in the disease-state gut microbiome that distinguish between diffuse adherent, enterotoxigenic, and enteropathogenic E. coli pathotypes. Therefore, our methodology and results should be highly relevant for diagnosing and treating diarrheal infections and have important applications in public health.
Assuntos
Infecções por Escherichia coli/microbiologia , Escherichia coli/metabolismo , Microbioma Gastrointestinal/fisiologia , Metagenoma , Estudos de Casos e Controles , Criança , Pré-Escolar , Diarreia/microbiologia , Surtos de Doenças , Equador , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Lactente , RNA Ribossômico 16S/genética , Virulência/genética , Fatores de Virulência/genéticaRESUMO
Uno de los retos más importantes de este siglo en la neurología genómica es construir mapas de expresión espacial de genes a lo largo de las distintas estructuras cerebrales con el fin de correlacionarlos con ciertas neuropatologías. Se analizaron los perfiles de transcripción de ocho genes HAS21 localizados en la región crítica del síndrome de Down en diferentes estructuras del cerebro humano normal. Se tomaron como referencia los valores de expresión de ocho genes HAS21/DSCR provenientes de experimentos de micromatrices de ADN de cerebros humanos normales y cuyos valores están disponibles en la base de datos del proyecto cerebro humano del Atlas del Cerebro del Allen Institute for Brain Sciences en Seattle, Washington (http://www.brainmap.org). Se determinó una expresión diferencial de estos genes HAS21/DSCR a lo largo de las estructuras localizadas en el lóbulo frontal, el lóbulo límbico y en los núcleos centrales. En el putamen, el núcleo caudado, el giro parahipocampal y en las áreas centrales se registraron los mayores niveles de transcripción global; estas áreas del cerebro parecen estar asociadas con diversos procesos de aprendizaje y de memoria. Se correlacionó la transcripción diferencial de genes DSCR con la localización cerebral y su potencial papel funcional.
One of the most important challenges of the 21st Century Neurology is to build gene expression profiles along the different structures of human brain trying to correlate them with some neuropathologies. The expression profiles of eight HAS21 genes located on the Down syndrome critical region in different structures of the normal human brain was analyzed. From DNA microarray experiments of normal human brains which are available in the free access human brain database of the Brain Atlas project of the Allen Institute for Brain Sciences in Seattle, Washington (http://www.brainmap.org) expression levels data of eight HSA21/DSCR genes along different structures of normal human brain were statistically analyzed. A differential expression of these genes HSA21/DSCR in some anatomic structures located in the frontal lobe, limbic lobe and cerebral central nuclei was registered. Putamen, caudate nucleus, parahipocampal gyro and central areas, showed high levels of transcription for those HSA21/DSCR genes included in the study; these areas of the brain appear to be associated with some processes of learning and memory. This study allowed us to correlate the differential transcription of DSCR genes, their structural localization and functional role in brain function.
Um dos maiores desafio deste século na neurologia genômica é construir mapas de expressão espacial de genes ao longo das diferentes estruturas cerebrais com o fim de correlacionálos com certas neuropatologias. Foram analisados os perfis de transcrição de oito genes HAS21 localizados na região crítica da síndrome de Down em diferentes estruturas do cérebro humano normal. Foram usados como referência os valores de expressão de oito genes HAS21/DSCR provenientes de experimentos de micromatrizes de ADN de cérebros humanos normais e cujos valores estão disponíveis no bando de dados do projeto cérebro humano do Atlas do Cérebro do Allen Institute for Brain Sciences em Seattle, Washington (http://www.brainmap.org). Determinouse uma expressão diferencial destes genes HAS21/DSCR ao longo das estruturas localizadas no lóbulo frontal, o lóbulo límbico e nos núcleos centrais. No putâmen, o núcleo caudado, o giro parahipocampal e nas áreas centrais foram registrados os maiores níveis de transcrição global; estas áreas do cérebro parecem estar associadas com diversos processos de aprendizagem e de memória. Correlacionouse a transcrição diferencial de genes DSCR com a localização cerebral e seu potencial papel funcional.
Assuntos
Humanos , Análise em Microsséries , Síndrome de Down , Biologia Computacional , Perfilação da Expressão Gênica , CérebroRESUMO
Evalúa aspectos de la estructura y funcionamiento de las Unidades de Rehidratación oral (URO) de la región III, Managua durante Enero de 1985, en cuanto, al nivel de conocimiento del personal de enfermería que maneja dichas unidades; dotación de materiales, equipos y educación en salud a familiares que acudieron en demanda de atención. El universo de estudio lo constituyeron las URO de la Región III, la recolección de datos se obtuvo a través de tres cuestionarios: el primero dirigido al personal de enfermería, el segundo para conocer del equipamiento en cada unidad y el tercero sobre la existencia de sales de rehidratación oral. Por medio de tabulación manual se procedió al análisis de la información, encontrándose que las URO presentaban dificultades en la disponibilidad de recursos materiales, que la formación del personal era insuficiente y orientadas hacia el aprendizaje de Normas Técnicas que a aspectos de educación sanitaria. Se recomienda la revisión de normas sobre la dotación de recursos a fin de establecer el equipo adecuado, evaluar la eficacia de la URO en relación con la rehidratación de los niños y la prevención de las complicaciones de las enfermedades diarréicas agudas, así como la revisión e implementación de un sistema de monitoreo y control que permita reforzar la función de adiestramiento y capacitación.