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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01TW007405-03
Application #
7483778
Study Section
Special Emphasis Panel (ZRG1-ICP-3 (51))
Program Officer
Jessup, Christine
Project Start
2006-09-15
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$106,595
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Public Health
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Mercado, Erik H; Piscoche, Cristian; Contreras, Carmen et al. (2016) Pathogenicity Island O-122 in enteropathogenic Escherichia coli strains is associated with diarrhea severity in children from Lima Peru. Int J Med Microbiol 306:231-6
Mosquito, Susan; Pons, Maria J; Riveros, Maribel et al. (2015) Diarrheagenic Escherichia coli phylogroups are associated with antibiotic resistance and duration of diarrheal episode. ScientificWorldJournal 2015:610403
Pons, Maria J; Mosquito, S; Gomes, C et al. (2014) Analysis of quinolone-resistance in commensal and diarrheagenic Escherichia coli isolates from infants in Lima, Peru. Trans R Soc Trop Med Hyg 108:22-8
Rivera, Fulton P; Medina, Anicia M; Aldasoro, Edelweiss et al. (2013) Genotypic characterization of enterotoxigenic Escherichia coli strains causing traveler's diarrhea. J Clin Microbiol 51:633-5
Durand, David; Ochoa, Theresa J; Bellomo, Sicilia M E et al. (2013) Detection of secretory immunoglobulin A in human colostrum as mucosal immune response against proteins of the type III secretion system of Salmonella, Shigella and enteropathogenic Escherichia coli. Pediatr Infect Dis J 32:1122-6
Barletta, Francesca; Ochoa, Theresa J; Cleary, Thomas G (2013) Multiplex real-time PCR (MRT-PCR) for diarrheagenic. Methods Mol Biol 943:307-14
Barletta, F; Mercado, E H; Lluque, A et al. (2013) Multiplex real-time PCR for detection of Campylobacter, Salmonella, and Shigella. J Clin Microbiol 51:2822-9
Rivera, F P; Sotelo, E; Morales, I et al. (2012) Short communication: Detection of Shiga toxin-producing Escherichia coli (STEC) in healthy cattle and pigs in Lima, Peru. J Dairy Sci 95:1166-9
Contreras, C A; Ochoa, T J; Ruiz, J et al. (2012) Genetic diversity of locus of enterocyte effacement genes of enteropathogenic Escherichia coli isolated from Peruvian children. J Med Microbiol 61:1114-20
Llanos, Alejandro; Lee, Jorge; Lopez, Francisco et al. (2012) Shiga toxin-producing Escherichia coli in Peruvian children with bloody diarrhea. Pediatr Infect Dis J 31:314-6

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