Project Summary
Diarrheal illness is the second most common cause of non-neonatal death among young children worldwide,
and is a major cause of morbidity. Current etiologic diagnosis of diarrhea relies on microbial detection, and
decisions for antibiotics commonly empiric. However, the majority of cases of diarrhea do not benefit from
antibiotic use, and testing for all potential pathogens is neither financially nor logistically feasible. Thus,
methods to improve the clinical management of pediatric diarrheal illness, including strategies for antimicrobial
and diagnostic stewardship, are needed. Clinical prediction rules are potential tools to address this need, and
in this K24 application, our overall goal is to explore strategies to improve clinical decision-making for diarrhea
management, through use of spatial-temporal data and biomarkers. Dr. Leung, the PI, is a physician-scientist
with training in clinical infectious diseases, immunology, microbiology, and epidemiology, with a focus on
enteric infections, especially those that cause diarrheal illness in children in limited-resource settings. He has
mentored over 40 patient-oriented researchers (PORs) since the start of his independent research program in
2014; additionally, he has co-mentored numerous PORs in collaboration with scientists and clinicians working
in low- and middle-income countries. Leveraging infrastructure already in place from three ongoing NIH-funded
awards (R01AI130378, R01AI135114, R01AI135115), as well as Gates Foundation-funded studies, he
proposes to augment his current POR by addressing the following aims: 1) To examine the use of spatial-
temporal data for individual-level clinical prediction of pediatric diarrhea, where the use of A) serosurveillance,
B) molecular diagnostic, and C) earth observation-derived data will be explored, and 2) To identify clinical use-
cases, and potential candidates, of fecal biomarkers that complement clinical decision support tools for
management of pediatric diarrhea, using both qualitative methods to examine end-user perspectives and
identify use-cases, and metabolomics and transcriptomics methods to identify candidate biomarkers. To
accomplish these aims, he has established a co-mentoring team of experienced investigators with diverse
expertise in statistical methods, biomarker discovery, and mentoring of POR investigators. This award will
provide protected time for Dr. Leung to improve and increase his mentoring capacity of POR trainees, expand
his expertise and experience in bioinformatics, and generate data for future projects to improve the
management and knowledge of pediatric diarrheal infections.