The impact of non-dysentery Shigella-associated diarrhea in children

PROJECT SUMMARY / ABSTRACT
Shigella is a primary cause of moderate-to-severe diarrhea in children living in impoverished areas of the world.
Shigella is known for causing dysentery (blood in stool). However, majority of the children infected with Shigella
present with watery diarrhea. The current World Health Organization (WHO) guidelines for treatment of
shigellosis (in the absence of a rapid, sensitive, simple and inexpensive diagnostic test) recommends treatment
with antibiotics when presence of visible blood in stool. Thus, the non-dysentery Shigella associated diarrhea
(NDSD) cases would not be treated with antibiotics. Absence of dysentery may not indicate a low risk of death
and does not exclude Shigella as a cause of diarrhea. In particularly vulnerable younger children or with
malnutrition, identification and treatment of Shigella infection might be life-saving. It may be hypothesized that
NDSD cases, if identified quickly, should be treated with antibiotics to improve survival and long-term
developmental potential in children. Identification of such cases will require a rapid test to document these
infections so that treatment can be initiated promptly, and evidence based.
To address these questions, we propose to conduct a prospective longitudinal case control study to understand
the pathophysiology of NDSD and the impact of NDSD in children compared to dysentery shigellosis. The
children seeking care in the hospital in Bangladesh with diarrhea (both dysentery and NDSD), that is positive for
Shigella and a third group with Shigella negative watery diarrhea will be enrolled and prospectively followed. Our
study has the following specific aims:
AIM 1. Determine morbidity and risk of hospitalization associated with NDSD cases and its impact on nutritional
status and cognitive development of the children.
AIM 2. Understand the impact of NDSD on gut barrier function, systemic and gut inflammation in children.
AIM 3. Evaluate if the simple and rapid test S-RLDT could be applicable for case detection and treatment of
shigellosis in the clinical settings of the rural hospitals of the endemic countries.
Collectively, our proposed research would broadly impact the field by understanding the pathophysiology of
NDSD and the impact of NDSD in child health. This study will help to understand if there is a need to change the
current guidelines of shigellosis treatment for better survival and development of the children. This study will also
validate a rapid test capable of identifying the patients who will benefit from antibiotics.

Grant Number: 5R01AI153399-05
NIH Institute/Center: NIH
Principal Investigator: Subhra Chakraborty