Dr. Ochoa is a pediatric infectious diseases specialist studying the effect of human milk protective factors on enteropathogens. Her goal is to become an independent investigator focusing on translational research in pathophysiology of enteric pathogens to improve the health of children with diarrhea! diseases. Persistent diarrhea accounts for many of diarrhea-related deaths in developing countries. The pathophysiology of persistent diarrhea is complex and is not completely understood. It is not clear why some children with diarrhea go on to develop a persistent illness, while others do not. Enteropathogenic E. coli (EPEC) are among the most important pathogens infecting infants worldwide. EPEC causes acute and persistent diarrhea. Previous studies have looked at the virulence of several EPEC proteins. However, there is a gap in the literature of the association and relevance of these proteins on the development of prolonged diarrhea. This study proposes to fill that critical gap. We hypothesize that variations in EPEC virulence genes and their expression determines the clinical manifestation of intestinal infections in children. We will explore the phenotypic and genotypic characteristics of EPEC strains from a prospective cohort of Peruvian children with diarrhea. In this study two aims will be addressed.
AIM 1. We will test the hypothesis that phenotypic variations in EPEC determines duration of diarrhea in children. Among EPEC strains isolated from Peruvian children with diarrhea we will determine the relationship between clinical illness (duration, severity and development of persistent diarrhea) and major virulence phenotypes. Three phenotypes will be evaluated: [1] Attachment/adherence to HEp2 cells, [2] Invasion to HEp2 cells, and [3] Immunosuppression (lymphocyte proliferation assay).
AIM 2. We will test the hypothesis that genotypic variations in EPEC determines duration of diarrhea in children. We will focus on genes relevant to: [1] Adhesion (bfpA, toxB, per, and subtypes of eae, espA, espB, espD, and tir), [2] Invasion (espG, ETT2) and [3] Immune suppression (efal/lifA). In addition, we will evaluate two other genes (espl, astA) that could relate to differences in clinical illness. Diarrheal disease is one of the most important public health problems in the world. Persistent diarrhea is associated with malnutrition and risk of death. Understanding why some children develop a prolonged illness may lead to effective interventions. ? ? ?
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