Diarrheal diseases are responsible for more than two billion cases every year and constitute one of the main global health challenges. The disease is particularly common in developing countries, where it disproportionally affects young children who, on average, get diarrhea three times a year. Diarrhea results from an infection in the intestinal tract, which can be caused by a variety of bacteria, viruses and eukaryotic parasites. In most studies, less than half of the diarrhea cases can be attributed to a known pathogen, partially due to the limitations of current detection approaches that i) only test a handful of known pathogens and/or ii) fail to differentiate among closely related species with different pathogenicity. Here, we propose to apply a novel genomic assay developed in our laboratory to screen 3,600 stool samples collected by the GEMS study in four countries from infants with diarrhea and matched controls. Our assay enables detection and characterization of all eukaryotic parasites present in a sample, regardless of whether they have been previously characterized (and may therefore reveal novel pathogens). It also provides sufficient resolution to differentiate closely-related organisms that are typically lumped together. Combined with a detailed characterization of the gut bacterial communities, our studies will provide a comprehensive perspective on the contribution of eukaryotic parasites to intestinal dysbiosis and diarrhea, and may highlight novel therapeutic avenues to fight this disease.

Public Health Relevance

Diarrheal diseases are responsible for more than half a million deaths every year and disproportionally affect young children in developing countries. Various bacteria, viruses and eukaryotic parasites have been associated with diarrhea but more than half of the disease cases cannot be unexplained by known pathogens. We propose to apply a novel genomic approach to screen thousands of stool samples, from infants with diarrhea and matched controls, for a wide variety of protozoa and parasitic worms to comprehensively characterize pathogens responsible for diarrhea in Sub-Saharan Africa and South Asia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI141859-01
Application #
9644204
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Joy, Deirdre A
Project Start
2018-11-08
Project End
2020-10-31
Budget Start
2018-11-08
Budget End
2019-10-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201