Identification of Novel Bio-markers for Environmental Enteropathy in Children Using an Evidence Based Approach

Summary

EE is increasingly recognized as a key factor underlying malnutrition, weakened immune response and impaired cognitive development in children in developing countries. Absence of a distinct biomarker of EE in the blood, urine or stool makes it difficult to study the impact of interventions against it. Biomarkers for EE have been challenging to find, partly because of our inadequate understanding of its pathophysiology. Investigators aim to identify novel biomarkers for EE, based on our hypothesis that EE is a result of two processes: 1) repeated exposure to enteric pathogens and environmental toxins leading to gut inflammation and 2) weaning on diets high in carbohydrates but low in proteins and fat, leading to atrophy of the intestinal mucosa. This leads to gut dysfunction, including leaky gut, small bowel stasis, bacterial overgrowth, decreased immune response to infections, and frequent diarrhea. The candidate biomarkers investigators have selected for our study (CRP, GLP- 2, Claudin 3, Reg-1, plasma amino acids profile, serum cytokine profile, Neopterin and Myeloperoxidase) are markers of inflammation, hormonal dysfunction and tight junction malfunction of the small intestines. The 'gold standard test' for EE will be direct histopathologic analysis of the duodenal mucosa, which will be available in a subset of study children undergoing upper GI endoscopy. For other study subjects, clinical surrogates for EE will be used to calculate the sensitivity and specificity of biomarkers being tested. These clinical surrogates of EE include HAZ and WAZ score \< 2 SD at 12 months and 15 months of age, and the worsening in HAZ and WAZ scores between 6, 9, 12 and 15 months of age. Investigators plan to study and compare duodenal biopsies from children with and without EE using cutting edge technologies including electron microscopy, immunofluorescence, and mRNA sequencing. This will allow direct correlation of the biomarkers in the blood, urine and stools with the histopathologic features of the gut mucosa. The mRNA sequencing of the gut tissue will allow us to identify new evidence-based biomarkers for EE, which could be further tested in the future.

This is a strong, multidisciplinary collaboration between investigators in Pakistan and the United States with expertise in complementary areas including chemokines, inflammation, gut architecture, infectious diseases, field studies, and technology development.

Conditions

• Malnutrition
• Enteropathy

Interventions

PROCEDURE

Upper Gastrointestinal Endoscopy

Procedure Upper gastro-intestinal endoscopic procedure involves collection of intestinal samples and it can be helpful in identifying the causes of malnutrition. Upon parental approval, the child along with two relatives will be provided transportation to Karachi, accommodation and the compensation for their time and expenses. For this procedure the child will be admitted to the hospital a day before the procedure till one day after the procedure. This procedure takes 30 minutes, requires general anesthesia and involves insertion of a flexible tube with a small TV camera and a light on one end and an eyepiece on the other. The endoscope will allow the doctor to examine the inside of certain tube-like structures in the body. Some tissue samples for laboratory testing will be taken.

Sponsors & Collaborators

• University of Reading

  collaborator OTHER

• Boston University

  collaborator OTHER

• Washington University School of Medicine

  collaborator OTHER

• University of Chicago

  collaborator OTHER

• University of Virginia

  collaborator OTHER

• Aga Khan University

  lead OTHER

Principal Investigators

• Syed Asad Ali · Aga Khan University

Eligibility

Min Age

6 Months

Max Age

24 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-01-31

Primary Completion

2015-04-30

Completion

2015-09-30

Countries

• Pakistan

Study Locations